Title: Immunogenicity and protective efficacy of a tuberculosis DNA vaccine co-expressing pro-apoptotic caspase-3
Authors: Gartner, Tatiana ×
Romano, Marta
Suin, Vanessa
Kalai, Michaeal
Korf, Hannelie
De Baetselier, Patrick
Huygen, Kris #
Issue Date: Mar-2008
Publisher: Butterworths
Series Title: Vaccine vol:26 issue:11 pages:1458-1470
Abstract: DNA vaccination is a potent means for inducing strong cell-mediated immune responses and protective immunity against viral, bacterial and parasite pathogens in rodents. In an attempt to increase cross-presentation through apoptosis, the DNA-encoding caspase-2 prodomain followed by wild-type or catalytically inactive mutated caspase-3 was inserted into a plasmid encoding the 32 kDa mycolyl transferase (Ag85A) from Mycobacterium tuberculosis. Transient transfection showed that the mutated caspase induced slow apoptosis, normal protein expression and NF-KB activation while wild-type caspase induced rapid apoptosis, lower protein expression and no NF-kappa B activation. Ag85A specific antibody production was increased by co-expressing the mutated and decreased by co-expressing the wild-type caspase. Vaccination with pro-apoptotic plasmids triggered more Ag85A specific IFN-gamma producing spleen cells, and more efficient IL-2 and IFN-gamma producing memory cells in spleen and lungs after M. tuberculosis challenge. Compared to DNA-encoding secreted Ag85A, vaccination with DNA co-expressing wild-type caspase increased protection after infection with M. tuberculosis, while vaccination with plasmid co-expressing mutated caspase was not protective, possibly due to the stimulation of IL-6, IL-10 and IL-17A production. (c) 2008 Elsevier Ltd. All rights reserved.
ISSN: 0264-410X
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Clinical and Experimental Endocrinology
× corresponding author
# (joint) last author

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